Early-Stage Squamous Cell Carcinoma of the Glottic Larynx Managed With Radiation Therapy
ROBERT L. FOOTE, M.D., Division ofRadiation Oncology; KERRY D. OLSEN, M.D., Department of Otorhinolaryngology; SUSAN J. KUNSELMAN, M.A., DANIEL J. SCHAID, Ph.D., Cancer Center Statistics; STEVEN J. BUSKIRK, M.D.,* GORDON L. GRADO, M.D.,t Department ofRadiation Oncology; JOHN D. EARLE, M.D., Division ofRadiation Oncology
Between January 1975 and December 1985, 45 patients with carcinoma in situ or invasive squamous cell carcinoma of the glottic larynx received radiation therapy at the Mayo Clinic. Local control in the entire group of 45 patients was 84 % (in 6 of 6 with carcinoma in situ and in 32 of 39 with invasive cancers). Three of seven patients (43%) with local recurrences underwent successfullarynx-preserving surgical procedures; thus, the rate of laryngeal preservation was 91 %. In our study of several treatment factors, including the duration of treatment, type of treatment (continuous course versus split course), photon energy (60CO versus 4-MV photons versus 6-MV photons), total dose, and dose per fraction, we found that only total dose of 6,300 cGy or more was associated with significantly improved local control (in 35 of 38 patients [92 % Two patients (4 %) died of uncontrolled delayed nodal metastases, one of which was preceded by a local recurrence. Severe laryngeal edema developed in two patients, associated with recurrent glottic carcinoma in one of them. No larynx was lost because of complications. In our current treatment recommendations, patients receive a total dose of 6,300 cGy in 28 fractions of 225 cGy each, administered in a continuous course with use of 6·MV photons.
n.
Early-stage squamous cell carcinoma of the glottic larynx can often be successfully managed with either radiation therapy or surgical intervention.t" Because the likelihood of cure is good with either modality, the choice of treatment should be based on several variables, including the patient's general health, occupation, and desires and the probability for a high rate oflocal control, an acceptable level of complications, and a good-quality voice. In this report, our objectives are to present our recent experience with use of radiation therapy for early-stage squamous cell carcinoma of the glottic larynx and to examine the relationship between various treatment factors and the likelihood of local control. *Mayo Clinic Jacksonville, Jacksonville, Florida. tMayo Clinic Scottsdale, Scottsdale, Arizona. Address reprint requests to Dr. R. L. Foote, Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 67:629-636, 1992
MATERIAL AND METHODS In this study, 45 patients with carcinoma in situ (6 patients) or invasive squamous cell carcinoma (39 patients) of the glottic larynx were treated, with curative intent, by irradiation at the Mayo Clinic between January 1975 and December 1985. The study group consisted of 39 men and 6 women. The median age at the time of treatment was 64.5 years (range, 41 to 88 years). No patient had previously received treatment; thus, radiation therapy was the first attempt at cure. The 1988 staging system established by the American Joint Committee on Cancer" was used to stage the carcinomas. Carcinoma in situ was staged similar to invasive disease. Stage Tllesions were subclassified as follows: TIa, involvement of one true vocal cord with or without involvement of the anterior commissure; and Tlb, involvement of both true vocal cords. Stage T2lesions were further subcategorized on the basis of the mobility of the vocal cords as 629
630
RADIATION THERAPY FOR GLOTIIC CARCINOMA
follows: T2a, normal mobility; and T2b, decreased mobility. The various T stages were also stratified by the anatomic extent of the tumor into three categories that corresponded to operative procedures used to treat vocal cord cancer at our institution during the time of the study (Table 1). In all 45 patients, irradiation was administered with use of megavoltage equipment and the following beams: 6OCO (in 13 patients), 4-MV photons (in 12), 6-MV photons (in 12), a combination of photon beams (in 2), and a combination of photons and electrons (in 6). Seventeen patients were treated with continuous-course irradiation administered in once-aday fractionation. The other 28 patients were treated with a planned split-course (3-week) technique. Patients were treated with the following field arrangements: ipsilateral field (in 1 patient), parallel-opposed lateral fields (in 37), or parallel-opposed lateral fields with an anterior boost field (in 7). Treatment was delivered with the patients in the supine position. Typically, the field borders extended from the middle of the thyroid notch to the bottom of the cricoid cartilage to 1 em behind the posterior aspect of the thyroid cartilage with anterior falloff. This field would correspond to an area of approximately 4 by 4 em to 6 by 6 em. The field borders were modified for each patient, depending on the anatomic extent of the particular lesion. Patients received total dosages in the range of 6,000 to 7,242 cGy (median, 6,500 cGy) at 178 to 236 cGy per fraction (median, 190 cGy), in five fractions per week. The time-dose-fractionation schedules used during the period of the study varied in accordance with the individual treating physician's preference. Two fields per day were treated in 35 patients, whereas only one field was treated each day in 10. Because of the small sample size, local control rates were compared by using Fischer's exact test for comparison of proportions." Survival distributions were estimated by using the Kaplan-Meier method."
Mayo Clin Proc, July 1992, Vol 67
Table I.-Characterization of Subgroups of Study Patients With Carcinoma of the Glottic Larynx and Recommended Surgical Management Suitablemanagement
Anatomicextent of lesion Lesion involvingmost of one entire true vocal cord but sparingthe anterior '/4; normalcord mobility; carcinomain situ Lesion involvingup to one entire' vocalcord and up to 1ts the contralateral true cord; no involvement of subglotticlarynx or false cord; normal cord mobility More extensivedisease than stated above
Transoralresection
Partial vertical laryngectomy
More extensivesurgical procedurethan stated above (total or neartotal laryngectomy or other)
in whom a recurrence developed. All patients with local recurrences underwent successful surgical salvage, three by partial vertical laryngectomy and four by total or near-total laryngectomy. Therefore, the laryngeal preservation rate was 91 % (41 of 45 patients). One of the seven patients in whom a local recurrence developed did not undergo totallaryngectomy until' 5 months after the recurrence was diagnosed because he had terminal metastatic prostatic and bladder cancer. He died free of glottic carcinoma 8 months after the total laryngectomy. The other six patients who had local recurrences after radiation therapy remained free of further local recurrence a median of 8.75 years (range, 4 to 9 years) after the salvage surgical procedures, although one patient subsequently died of delayed, uncontrolled cervical nodal metastatic disease. The rate of local control for the entire
RESULTS At the time of the analysis, 24 patients (53%) were alive and had no evidence of glottic carcinoma. The median follow-up was 9.2 years (range, 1.5 to 15 years). Nineteen patients (42%) died of causes unrelated to the glottic carcinoma, without recurrence of the cancer. The median follow-up was 5.7 years (range, 0.5 to 14 years; more than 3 years in 15 of the 19 patients). Two patients (4%) died of delayed, uncontrolled metastatic involvement of cervical nodes, one of whom had a preceding local recurrence. No patient died of a local recurrence. Furthermore, no distant metastatic lesions developed. Stage of Carcinoma-s- The local control, death due to glottic cancer, and laryngeal preservation rates are shown by stage in Table 2. The median time to local recurrence was 20.4 months (range, 6 to 31.9 months) for the seven patients
Table 2.-Rates of Local Control, Death Due to Glottic Cancer, and Laryngeal Preservation, Stratified by Stage of Carcinoma
Stage Tla Tlb All Tl T2a T2b All T2 Total
No. of patients
Local control No. %
30
24
41 2 2 4 45
35 85 1 50 2 100 3 75 38 84
11
80
11 100
*Including surgicalsalvage.
Death due to glotticcancer No. % 1 0 1 1 0 1 2
3 2 50 25 4
Laryngeal preservation* No. % 27
90
11 100
38 93 1 50 2 100 3 75 41 91
Mayo ClinProc,July 1992, Vol 67
RADIATION THERAPY FOR GLOTTIC CARCINOMA
Table 3.-Rates of Local Control, Death Due to Glottic Cancer, and Laryngeal Preservation, Stratified by Surgical-Anatomic Extent of Carcinoma Surgical procedure* TO PVL TL,NTL,O Total
Local control No. of patients No. % 8 29 8 45
8 100 22 76 8 100 38 84
Death due to Laryngeal glotticcancer preservationt No. % No. % 0 2 0 2
7 4
8 100 25 86 8 100 41 91
*NTL =near-totallaryngectomy; 0 =other;PVL =partial vertical laryngectomy; TL = total laryngectomy; TO = transoralresection. tlncluding surgical salvage. group of 45 patients was 84%; it was 85% for Tllesions and 75% for T2lesions. Extent of Carcinoma-s- The rates of local control, death due to glottic cancer, and laryngeal preservation are stratified by the surgical-anatomic extent of the cancer in Table 3. The data were analyzed in this manner because the extent of tumor variation within the TI stage is considerable. By grouping the patients in this way, we expected an accurate reflection of the extent of the lesion and the corresponding projected outcome after radiation therapy. This collective analysis was for illustrative purposes only; we would not recommend a total laryngectomy for early-stage glottic cancer. The 16 patients who could have undergone a transoral resection (6 with carcinoma in situ) or operations more extensive than a partial vertical laryngectomy had no local recurrences. Among the total group of 45 patients, the rate of local control was 84%, and the rate of laryngeal preservation after surgical salvage was 91%. Treatment Factors.-The local control stratified by several treatment factors, including the overall duration of treatment' type of treatment (continuous-course versus splitcourse regimen), photon energy, total dose, and dose per fraction, is shown in Table 4. When the data were analyzed by photon energy, the two patients treated with a combination of 4-MV photons and 6OCO y-rays were combined with the group of patients treated only with 4-MV photons because most of the treatment was with 4-MV photons. Likewise, the six patients treated with 4-MV or 6-MV photons and an electron beam boost were grouped on the basis of photon energy because most of the treatment was with photons. Of the various treatment factors analyzed by univariate statistical analysis, only total dose was significantly related to local control. Dose of lrradiation.-The various patient, tumor, and treatment factors are stratified by level of dose of radiation therapy in Table 5. Even though the number of patients was small, the factors seemed to be evenly distributed between
631
Table 4.-Local Control of Carcinoma of the Glottic Larynx, Stratified by Overall Duration of Treatment, Type of Treatment, Photon Energy, Total Dose, and Dose per Fraction No. of patients
Local control No. %
Two-sided P value
12 33
12 100 26 79
0.164
Type of treatment Continuouscourse Split course
17 28
16 22
94 79
0.227
Photon energy 60CO 4MV 6MV
13 16 16
10 77 12 75 16 100
0.082
7 38
3 35
43 92
0.007
35 10
28 80 10 100
0.320
Treatment factor Overall duration of treatment (days)
ROBERT L. FOOTE, M.D., Division ofRadiation Oncology; KERRY D. OLSEN, M.D., Department of Otorhinolaryngology; SUSAN J. KUNSELMAN, M.A., DANIEL J. SCHAID, Ph.D., Cancer Center Statistics; STEVEN J. BUSKIRK, M.D.,* GORDON L. GRADO, M.D.,t Department ofRadiation Oncology; JOHN D. EARLE, M.D., Division ofRadiation Oncology
Between January 1975 and December 1985, 45 patients with carcinoma in situ or invasive squamous cell carcinoma of the glottic larynx received radiation therapy at the Mayo Clinic. Local control in the entire group of 45 patients was 84 % (in 6 of 6 with carcinoma in situ and in 32 of 39 with invasive cancers). Three of seven patients (43%) with local recurrences underwent successfullarynx-preserving surgical procedures; thus, the rate of laryngeal preservation was 91 %. In our study of several treatment factors, including the duration of treatment, type of treatment (continuous course versus split course), photon energy (60CO versus 4-MV photons versus 6-MV photons), total dose, and dose per fraction, we found that only total dose of 6,300 cGy or more was associated with significantly improved local control (in 35 of 38 patients [92 % Two patients (4 %) died of uncontrolled delayed nodal metastases, one of which was preceded by a local recurrence. Severe laryngeal edema developed in two patients, associated with recurrent glottic carcinoma in one of them. No larynx was lost because of complications. In our current treatment recommendations, patients receive a total dose of 6,300 cGy in 28 fractions of 225 cGy each, administered in a continuous course with use of 6·MV photons.
n.
Early-stage squamous cell carcinoma of the glottic larynx can often be successfully managed with either radiation therapy or surgical intervention.t" Because the likelihood of cure is good with either modality, the choice of treatment should be based on several variables, including the patient's general health, occupation, and desires and the probability for a high rate oflocal control, an acceptable level of complications, and a good-quality voice. In this report, our objectives are to present our recent experience with use of radiation therapy for early-stage squamous cell carcinoma of the glottic larynx and to examine the relationship between various treatment factors and the likelihood of local control. *Mayo Clinic Jacksonville, Jacksonville, Florida. tMayo Clinic Scottsdale, Scottsdale, Arizona. Address reprint requests to Dr. R. L. Foote, Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 67:629-636, 1992
MATERIAL AND METHODS In this study, 45 patients with carcinoma in situ (6 patients) or invasive squamous cell carcinoma (39 patients) of the glottic larynx were treated, with curative intent, by irradiation at the Mayo Clinic between January 1975 and December 1985. The study group consisted of 39 men and 6 women. The median age at the time of treatment was 64.5 years (range, 41 to 88 years). No patient had previously received treatment; thus, radiation therapy was the first attempt at cure. The 1988 staging system established by the American Joint Committee on Cancer" was used to stage the carcinomas. Carcinoma in situ was staged similar to invasive disease. Stage Tllesions were subclassified as follows: TIa, involvement of one true vocal cord with or without involvement of the anterior commissure; and Tlb, involvement of both true vocal cords. Stage T2lesions were further subcategorized on the basis of the mobility of the vocal cords as 629
630
RADIATION THERAPY FOR GLOTIIC CARCINOMA
follows: T2a, normal mobility; and T2b, decreased mobility. The various T stages were also stratified by the anatomic extent of the tumor into three categories that corresponded to operative procedures used to treat vocal cord cancer at our institution during the time of the study (Table 1). In all 45 patients, irradiation was administered with use of megavoltage equipment and the following beams: 6OCO (in 13 patients), 4-MV photons (in 12), 6-MV photons (in 12), a combination of photon beams (in 2), and a combination of photons and electrons (in 6). Seventeen patients were treated with continuous-course irradiation administered in once-aday fractionation. The other 28 patients were treated with a planned split-course (3-week) technique. Patients were treated with the following field arrangements: ipsilateral field (in 1 patient), parallel-opposed lateral fields (in 37), or parallel-opposed lateral fields with an anterior boost field (in 7). Treatment was delivered with the patients in the supine position. Typically, the field borders extended from the middle of the thyroid notch to the bottom of the cricoid cartilage to 1 em behind the posterior aspect of the thyroid cartilage with anterior falloff. This field would correspond to an area of approximately 4 by 4 em to 6 by 6 em. The field borders were modified for each patient, depending on the anatomic extent of the particular lesion. Patients received total dosages in the range of 6,000 to 7,242 cGy (median, 6,500 cGy) at 178 to 236 cGy per fraction (median, 190 cGy), in five fractions per week. The time-dose-fractionation schedules used during the period of the study varied in accordance with the individual treating physician's preference. Two fields per day were treated in 35 patients, whereas only one field was treated each day in 10. Because of the small sample size, local control rates were compared by using Fischer's exact test for comparison of proportions." Survival distributions were estimated by using the Kaplan-Meier method."
Mayo Clin Proc, July 1992, Vol 67
Table I.-Characterization of Subgroups of Study Patients With Carcinoma of the Glottic Larynx and Recommended Surgical Management Suitablemanagement
Anatomicextent of lesion Lesion involvingmost of one entire true vocal cord but sparingthe anterior '/4; normalcord mobility; carcinomain situ Lesion involvingup to one entire' vocalcord and up to 1ts the contralateral true cord; no involvement of subglotticlarynx or false cord; normal cord mobility More extensivedisease than stated above
Transoralresection
Partial vertical laryngectomy
More extensivesurgical procedurethan stated above (total or neartotal laryngectomy or other)
in whom a recurrence developed. All patients with local recurrences underwent successful surgical salvage, three by partial vertical laryngectomy and four by total or near-total laryngectomy. Therefore, the laryngeal preservation rate was 91 % (41 of 45 patients). One of the seven patients in whom a local recurrence developed did not undergo totallaryngectomy until' 5 months after the recurrence was diagnosed because he had terminal metastatic prostatic and bladder cancer. He died free of glottic carcinoma 8 months after the total laryngectomy. The other six patients who had local recurrences after radiation therapy remained free of further local recurrence a median of 8.75 years (range, 4 to 9 years) after the salvage surgical procedures, although one patient subsequently died of delayed, uncontrolled cervical nodal metastatic disease. The rate of local control for the entire
RESULTS At the time of the analysis, 24 patients (53%) were alive and had no evidence of glottic carcinoma. The median follow-up was 9.2 years (range, 1.5 to 15 years). Nineteen patients (42%) died of causes unrelated to the glottic carcinoma, without recurrence of the cancer. The median follow-up was 5.7 years (range, 0.5 to 14 years; more than 3 years in 15 of the 19 patients). Two patients (4%) died of delayed, uncontrolled metastatic involvement of cervical nodes, one of whom had a preceding local recurrence. No patient died of a local recurrence. Furthermore, no distant metastatic lesions developed. Stage of Carcinoma-s- The local control, death due to glottic cancer, and laryngeal preservation rates are shown by stage in Table 2. The median time to local recurrence was 20.4 months (range, 6 to 31.9 months) for the seven patients
Table 2.-Rates of Local Control, Death Due to Glottic Cancer, and Laryngeal Preservation, Stratified by Stage of Carcinoma
Stage Tla Tlb All Tl T2a T2b All T2 Total
No. of patients
Local control No. %
30
24
41 2 2 4 45
35 85 1 50 2 100 3 75 38 84
11
80
11 100
*Including surgicalsalvage.
Death due to glotticcancer No. % 1 0 1 1 0 1 2
3 2 50 25 4
Laryngeal preservation* No. % 27
90
11 100
38 93 1 50 2 100 3 75 41 91
Mayo ClinProc,July 1992, Vol 67
RADIATION THERAPY FOR GLOTTIC CARCINOMA
Table 3.-Rates of Local Control, Death Due to Glottic Cancer, and Laryngeal Preservation, Stratified by Surgical-Anatomic Extent of Carcinoma Surgical procedure* TO PVL TL,NTL,O Total
Local control No. of patients No. % 8 29 8 45
8 100 22 76 8 100 38 84
Death due to Laryngeal glotticcancer preservationt No. % No. % 0 2 0 2
7 4
8 100 25 86 8 100 41 91
*NTL =near-totallaryngectomy; 0 =other;PVL =partial vertical laryngectomy; TL = total laryngectomy; TO = transoralresection. tlncluding surgical salvage. group of 45 patients was 84%; it was 85% for Tllesions and 75% for T2lesions. Extent of Carcinoma-s- The rates of local control, death due to glottic cancer, and laryngeal preservation are stratified by the surgical-anatomic extent of the cancer in Table 3. The data were analyzed in this manner because the extent of tumor variation within the TI stage is considerable. By grouping the patients in this way, we expected an accurate reflection of the extent of the lesion and the corresponding projected outcome after radiation therapy. This collective analysis was for illustrative purposes only; we would not recommend a total laryngectomy for early-stage glottic cancer. The 16 patients who could have undergone a transoral resection (6 with carcinoma in situ) or operations more extensive than a partial vertical laryngectomy had no local recurrences. Among the total group of 45 patients, the rate of local control was 84%, and the rate of laryngeal preservation after surgical salvage was 91%. Treatment Factors.-The local control stratified by several treatment factors, including the overall duration of treatment' type of treatment (continuous-course versus splitcourse regimen), photon energy, total dose, and dose per fraction, is shown in Table 4. When the data were analyzed by photon energy, the two patients treated with a combination of 4-MV photons and 6OCO y-rays were combined with the group of patients treated only with 4-MV photons because most of the treatment was with 4-MV photons. Likewise, the six patients treated with 4-MV or 6-MV photons and an electron beam boost were grouped on the basis of photon energy because most of the treatment was with photons. Of the various treatment factors analyzed by univariate statistical analysis, only total dose was significantly related to local control. Dose of lrradiation.-The various patient, tumor, and treatment factors are stratified by level of dose of radiation therapy in Table 5. Even though the number of patients was small, the factors seemed to be evenly distributed between
631
Table 4.-Local Control of Carcinoma of the Glottic Larynx, Stratified by Overall Duration of Treatment, Type of Treatment, Photon Energy, Total Dose, and Dose per Fraction No. of patients
Local control No. %
Two-sided P value
12 33
12 100 26 79
0.164
Type of treatment Continuouscourse Split course
17 28
16 22
94 79
0.227
Photon energy 60CO 4MV 6MV
13 16 16
10 77 12 75 16 100
0.082
7 38
3 35
43 92
0.007
35 10
28 80 10 100
0.320
Treatment factor Overall duration of treatment (days)
